This Lung Cancer SPORE application is a competing renewal application submitted by the Vanderbilt-lngram Cancer Center and its affiliated institutions. Cancer is now the number one killer of Americans, and lung cancer is the number one cause of cancer death, causing the deaths of more people than breast, colon, and prostate cancers combined. The Vanderbilt-lngram Cancer Center SPORE application in lung cancer is composed of investigators with expertise in proteomics, cellular and molecular biology, epidemiology, pathology, pulmonary medicine and medical, radiation, and surgical oncology committed to translational research with the goal of reducing the incidence, morbidity and mortality of lung cancer. We are applying a broad range of state-of-the-art technologies, including leading edge protein mass spectrometry, expertise in signal transduction, and in eicosanoid biology, as well as innovative bioinformatics and statistical analyses to this problem. We have assembled a multidisciplinary team of internationally recognized basic and clinical investigators into a cohesive program with a history of progress in the translation of laboratory findings into the clinic and back, as well as a track record of extensive collaborations with the other lung SPOREs, multiple cooperative groups, as well as the two other SPOREs at Vanderbilt. We have demonstrated flexibility and responsiveness in our program to optimize achieving the broader goals of our SPORE. The overall goal of our program is to define complex pathways and important intermediates in these pathways to help in the early detection and optimal treatment of patients with lung cancer. Our program is focused on elements of these pathways of potential utility both as clinically useful biomarkers for early detection, prediction and prognostication, but also as potential direct therapeutic targets.